Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors

Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P2 binding pocket of human mast cell tryptase, while building in a high degree of selectivity over human trypsin and other serine proteases.